Abstract
A group of mixed-ligand Pt(II) complexes bearing acetylacetonate and sulphur ligands were recently developed in the University of Lecce as a new class of prospective anticancer agents that manifested promising pharma-cological properties in preliminary in vitro and in vivo tests. Though modelled on the basis of cisplatin, these Pt(II) complexes turned out to exhibit a profoundly distinct mode of action as they were found to act mainly on non-genomic targets rather than on DNA. Accordingly, we have explored here their reactions with two representative model proteins through an established ESI–MS procedure with the aim to describe their general interaction mechanism with protein targets. A pronounced reactivity with the tested proteins was indeed documented; the nature of the resulting metallodrug-protein interactions could be characterised in depth in the various cases. Preferential binding to protein targets compared to DNA is supported by independent ICP-OES measurements. The implications of these findings are discussed.
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Acknowledgements
We thank Dr. M. Severi and Prof. R. Udisti for ICP-OES measurements. AP and LM gratefully acknowledge the financial support from Beneficentia Stiftung (Vaduz, Liechtenstein), Ente Cassa di Risparmio di Firenze and AIRC (IG-16049). The Consorzio Interuniversitario di Ricerca in Chimica dei Metalli nei Sistemi Biologici (CIRCMSB), Bari, Italy and the PON (Programma Operativo Nazionale) grant 254/Ric. Potenziamento del ‘‘Centro Ricerche per la Salute dell’Uomo e dell’Ambiente” Code PONa3_00334 are also acknowledged. C.G. and T.M. acknowledge University of Pisa for PRA_2017_25 Grant. T.M. thanks AIRC-FIRC (Fondazione Italiana per la Ricerca sul Cancro, 3-years Fellowship for Italy, Project Code: 18044).
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Marzo, T., De Pascali, S.A., Gabbiani, C. et al. ESI–MS studies of the reactions of novel platinum(II) complexes containing O,O′-chelated acetylacetonate and sulfur ligands with selected model proteins. Biometals 30, 609–614 (2017). https://doi.org/10.1007/s10534-017-0031-0
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DOI: https://doi.org/10.1007/s10534-017-0031-0